Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents
A novel library of 1,3,4-thiadazoloaryl based pyrimidine-thiazole derivatives (10a-j) was synthesized and their chemical structures were confirmed by 1HNMR, 13CNMR, and mass spectral data. in silico ADME studies have demonstrated that all these compounds have a good pharmacokinetic profile. Further,...
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| Format: | Article |
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Elsevier
2024-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624000304 |
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| author | Ramesh Boddiboyena Gattu Sridhar G. Nagendra Reddy Nareshvarma Seelam Monima Sarma Deepti Kolli Mura Reddy Gudisela |
| author_facet | Ramesh Boddiboyena Gattu Sridhar G. Nagendra Reddy Nareshvarma Seelam Monima Sarma Deepti Kolli Mura Reddy Gudisela |
| author_sort | Ramesh Boddiboyena |
| collection | DOAJ |
| description | A novel library of 1,3,4-thiadazoloaryl based pyrimidine-thiazole derivatives (10a-j) was synthesized and their chemical structures were confirmed by 1HNMR, 13CNMR, and mass spectral data. in silico ADME studies have demonstrated that all these compounds have a good pharmacokinetic profile. Further, these compounds were evaluated for their anticancer activity against a panel of human cancer cell lines such as prostate (PC3 and DU-145), lung (A549), and breast (MCF-7). The outcome results were compared with the standard reference as etoposide. Most of the tested compounds demonstrated remarkable anticancer activities, with IC50 values ranging from 0.01 ± 0.0017 µM to 23.6 ± 8.43 µM, where standard showed IC50 values from 1.97 ± 0.45 µM to 3.08 ± 0.135 µM, respectively. Particularly, these compounds 10a, 10b, 10c, 10d, 10e, and 10j displayed more prominent anticancer activities as etoposide. Molecular docking studies of the synthesized compounds were carried out against SARM (PDB ID: 3V49) and Abl-Tyrosine kinase (PDB ID: 1IEP), in which 10b and 10 h showed comparable dock scores of −7.3 and −7.5 against SARM (PDB ID: 3V49) and 10b and 10c −8.5 and −7.7 against Abl-Tyrosine kinase (PDB ID: 1IEP). |
| first_indexed | 2024-03-08T06:21:14Z |
| format | Article |
| id | doaj.art-4f8f8906ea214259bbea45b2b881bab8 |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-08T06:21:14Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-4f8f8906ea214259bbea45b2b881bab82024-02-04T04:44:33ZengElsevierResults in Chemistry2211-71562024-01-017101334Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agentsRamesh Boddiboyena0Gattu Sridhar1G. Nagendra Reddy2Nareshvarma Seelam3Monima Sarma4Deepti Kolli5Mura Reddy Gudisela6Department of Chemistry, Koneru Lakshmaiah Education Foundation (KLEF), Vaddeswaram, Guntur 522 502, India; Sigma-Aldrich Chemicals Pvt. Ltd., (Subsidiary of Merck KGaA), Bangalore 560 100, IndiaDepartment of Chemistry, Kakatiya Institute of Technology and Science, Warangal, Telangana, IndiaDepartment of Chemistry, Koneru Lakshmaiah Education Foundation (KLEF), Vaddeswaram, Guntur 522 502, IndiaDepartment of Chemistry, Koneru Lakshmaiah Education Foundation (KLEF), Vaddeswaram, Guntur 522 502, IndiaDepartment of Chemistry, Koneru Lakshmaiah Education Foundation (KLEF), Vaddeswaram, Guntur 522 502, India; Corresponding author.Department of Chemistry, Koneru Lakshmaiah Education Foundation (KLEF), Vaddeswaram, Guntur 522 502, IndiaTagoor Laboratories Pvt. Ltd. IDA, Jeedimetla, Hyderabad 500 055, IndiaA novel library of 1,3,4-thiadazoloaryl based pyrimidine-thiazole derivatives (10a-j) was synthesized and their chemical structures were confirmed by 1HNMR, 13CNMR, and mass spectral data. in silico ADME studies have demonstrated that all these compounds have a good pharmacokinetic profile. Further, these compounds were evaluated for their anticancer activity against a panel of human cancer cell lines such as prostate (PC3 and DU-145), lung (A549), and breast (MCF-7). The outcome results were compared with the standard reference as etoposide. Most of the tested compounds demonstrated remarkable anticancer activities, with IC50 values ranging from 0.01 ± 0.0017 µM to 23.6 ± 8.43 µM, where standard showed IC50 values from 1.97 ± 0.45 µM to 3.08 ± 0.135 µM, respectively. Particularly, these compounds 10a, 10b, 10c, 10d, 10e, and 10j displayed more prominent anticancer activities as etoposide. Molecular docking studies of the synthesized compounds were carried out against SARM (PDB ID: 3V49) and Abl-Tyrosine kinase (PDB ID: 1IEP), in which 10b and 10 h showed comparable dock scores of −7.3 and −7.5 against SARM (PDB ID: 3V49) and 10b and 10c −8.5 and −7.7 against Abl-Tyrosine kinase (PDB ID: 1IEP).http://www.sciencedirect.com/science/article/pii/S2211715624000304Dasatinib1,3-ThiazolesAcetazolamide1,3,4-ThiadazoleSARAnticancer |
| spellingShingle | Ramesh Boddiboyena Gattu Sridhar G. Nagendra Reddy Nareshvarma Seelam Monima Sarma Deepti Kolli Mura Reddy Gudisela Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents Results in Chemistry Dasatinib 1,3-Thiazoles Acetazolamide 1,3,4-Thiadazole SAR Anticancer |
| title | Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents |
| title_full | Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents |
| title_fullStr | Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents |
| title_full_unstemmed | Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents |
| title_short | Design, synthesis, anticancer evaluation, molecular docking and in silico ADME analysis of novel substituted 1,3,4-thiadazoloaryl incorporated pyrimidine-thiazole derivatives as propitious anticancer agents |
| title_sort | design synthesis anticancer evaluation molecular docking and in silico adme analysis of novel substituted 1 3 4 thiadazoloaryl incorporated pyrimidine thiazole derivatives as propitious anticancer agents |
| topic | Dasatinib 1,3-Thiazoles Acetazolamide 1,3,4-Thiadazole SAR Anticancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624000304 |
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